PF 04531083

Name: PF 04531083
Brand: MedChemExpress
SKU: HY-105283
Rating: 4.5 (1 reviews)

Cat. No.: HY-105283 Purity: 98.96%: Data Sheet
SDS

COA
Handling Instructions Technical Support

Solubility

In Vivo Dissolution Calculator

PF 04531083 is an orally active and selective Na_V1.8 blocker with an IC₅₀ of 0.7 μM. PF 04531083 is a blood-brain barrier (BBB) penetrant compound. PF 04531083 can be used for the research of respiratory system and neuropathic/inflammatory pain.

For research use only. We do not sell to patients.

PF 04531083 Chemical Structure

CAS No. : 1079400-07-9

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 105	In-stock	Estimated Time of Arrival: April 10
Solution
10 mM * 1 mL in DMSO	USD 110	In-stock	Estimated Time of Arrival: April 10
Solid
5 mg	USD 100	In-stock	Estimated Time of Arrival: April 10
10 mg	USD 180	In-stock	Estimated Time of Arrival: April 10
25 mg	USD 280	In-stock	Estimated Time of Arrival: April 10
50 mg	USD 420	In-stock	Estimated Time of Arrival: April 10
100 mg	USD 590	In-stock	Estimated Time of Arrival: April 10
200 mg		Get quote
500 mg		Get quote

Get it by tomorrow April 10 for select sizes. Order within 3 hrs 39 mins.

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Customer Review

Based on 1 publication(s) in Google Scholar

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View All Sodium Channel Isoform Specific Products:

View All Isoforms

Na_v1.1 Na_v1.2 Na_v1.3 Na_v1.4 Na_v1.5 Na_v1.6 Na_v1.7 Na_v1.8

Biological Activity
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target^[1]

Na_v1.8

Cellular Effect

Cell Line	Type	Value	Description	References
HEK293	IC₅₀	0.19 μM Compound: 13	Inhibition of human Nav1.8/beta1 expressed in HEK293 cells by manual patch clamp electrophysiology Inhibition of human Nav1.8/beta1 expressed in HEK293 cells by manual patch clamp electrophysiology	[PMID: 26101568]
HEK293	IC₅₀	0.7 μM Compound: 13	Inhibition of human Nav1.8 expressed in HEK293 cells assessed as reduction in blue fluorescent signal by VSP-FRET assay Inhibition of human Nav1.8 expressed in HEK293 cells assessed as reduction in blue fluorescent signal by VSP-FRET assay	[PMID: 26101568]
HEK293	IC₅₀	36 μM Compound: 13	Inhibition of human Nav1.7 expressed in HEK293 cells by FRET assay Inhibition of human Nav1.7 expressed in HEK293 cells by FRET assay	[PMID: 26101568]
HEK293	IC₅₀	37 μM Compound: 13	Inhibition of human Nav1.1 expressed in HEK293 cells by IonWorks Quattro selectivity assay Inhibition of human Nav1.1 expressed in HEK293 cells by IonWorks Quattro selectivity assay	[PMID: 26101568]
HEK293	IC₅₀	37 μM Compound: 13	Inhibition of human Nav1.5 expressed in HEK293 cells by IonWorks Quattro selectivity assay Inhibition of human Nav1.5 expressed in HEK293 cells by IonWorks Quattro selectivity assay	[PMID: 26101568]

In Vitro

PF 04531083 (1 μM) stimulates baseline activity by ~50% and the firing response to 10% CO₂ in chemosensitive retrotrapezoid nucleus (RTN) neuron in a slice from a Tcf4^tr/+ mice^[3].
PF 04531083 blocks human Na_v1.8, hNa_v1.1, hNa_v1.5, hNa_v1.7, TTX-r rat DRG, TTX-R hDRG, hERG with IC₅₀ values of 0.19, 37, 37, 36, 0.54, 0.2, >30 μM, respectively^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Parmacokinetics

Species	Dose	Route	Indicator	value
Rat	1 mg/kg	i.v.	T_1/2	3.9 hr
Rat	2 mg/kg	p.o.	T_1/2	N.D.
Rat	1 mg/kg	i.v.	T_max	-
Rat	2 mg/kg	p.o.	T_max	1.3 hr
Rat	1 mg/kg	i.v.	CL	6.7 mL/min/kg
Rat	2 mg/kg	p.o.	CL	11.4 mL/min/kg
Rat	1 mg/kg	i.v.	V_d	2.25 L/kg
Rat	2 mg/kg	p.o.	V_d	-
Rat	1 mg/kg	i.v.	F	-
Rat	2 mg/kg	p.o.	F	59 %

In Vivo

PF 04531083 (1 mg/kg, i.v.; or 2 mg/kg, p.o.) is a low clearance compound with good bioavailability ∼60% in rats^[2].
PF 04531083 (40 mg/kg; 1.5 h) is efficacious in the tibial nerve transection (TNT) induced mechanical allodynia model in rat^[2].
PF 04531083 inhibits native tetrodotoxin-resistant (TTX-R) currents in rodent dorsal root ganglion (DRG) neurons with an IC₅₀ of 0.54 μM^[2].
PF 04531083 (40 mg/kg; 1.5 h) improves baseline breathing in Tcf4^tr/+ mice^[3].
PF 04531083 (30 min before test) improves behavioral abnormalities associated with Pitt-Hopkins syndrome (PTHS) in Tcf4^tr/+ mice^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Tcf4^+/+ and Tcf4^tr/+ mice ^[3]
Dosage:	40 mg/kg
Administration:	Intraperitoneal injection (i.p.), 1.5 h before test
Result:	Decreased episodes of hyperventilation, increased the occurrence of spontaneous sighs, diminished duration of post-sigh apnea and improved the CO₂ minute ventilatory response in Tcf4^tr/+ mice. Showed stable respiratory activity in Tcf4^+/+ mice. Showed a robust increase in respiratory activity (62.5% increase in minute ventilation from 3 to 7% CO₂) in Tcf4^tr/+ pups.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase
NCT01012310	Pfizer	Healthy Volunteers	November 2009	Phase 1
NCT01512160	Pfizer	Post-surgical Dental Pain	October 2011	Phase 2
NCT01127906	Pfizer	Healthy	June 2010	Phase 1
NCT01119235	Pfizer	Chronic Pain	May 2010	Phase 1
NCT01103739	Pfizer	Chronic Pain	March 2010	Phase 1
NCT00992316	Pfizer	Pain	August 2009

Molecular Weight

357.79

Formula

C₁₇H₁₆ClN₅O₂

CAS No.

1079400-07-9

Appearance

Solid

Color

Light yellow to yellow

SMILES

ClC1=CC=C(OC)C=C1C2=C(N=C(NC(C3=CC=NN3C)=O)C=C2)N

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL (279.49 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.7949 mL	13.9747 mL	27.9494 mL
5 mM	0.5590 mL	2.7949 mL	5.5899 mL
10 mM	0.2795 mL	1.3975 mL	2.7949 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (5.81 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (5.81 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (5.81 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, PEG300/PEG400, Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Purity & Documentation

Purity: 98.96%

Select Batch:

Data Sheet (279 KB) SDS (392 KB)

COA (254 KB) HNMR (273 KB) LCMS (267 KB)

Handling Instructions (2659 KB)

References

[1]. Yekkirala AS, et al. Breaking barriers to novel analgesic drug development. Nat Rev Drug Discov. 2017 Aug;16(8):545-564. [Content Brief]

[2]. Bagal SK, et al. Discovery and Optimization of Selective Nav1.8 Modulator Series That Demonstrate Efficacy in Preclinical Models of Pain. ACS Med Chem Lett. 2015 Apr 29;6(6):650-4. [Content Brief]

[3]. Cleary CM, et al. Disordered breathing in a Pitt-Hopkins syndrome model involves Phox2b-expressing parafacial neurons and aberrant Nav1.8 expression. Nat Commun. 2021 Oct 13;12(1):5962. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.7949 mL	13.9747 mL	27.9494 mL	69.8734 mL
	5 mM	0.5590 mL	2.7949 mL	5.5899 mL	13.9747 mL
	10 mM	0.2795 mL	1.3975 mL	2.7949 mL	6.9873 mL
	15 mM	0.1863 mL	0.9316 mL	1.8633 mL	4.6582 mL
	20 mM	0.1397 mL	0.6987 mL	1.3975 mL	3.4937 mL
	25 mM	0.1118 mL	0.5590 mL	1.1180 mL	2.7949 mL
	30 mM	0.0932 mL	0.4658 mL	0.9316 mL	2.3291 mL
	40 mM	0.0699 mL	0.3494 mL	0.6987 mL	1.7468 mL
	50 mM	0.0559 mL	0.2795 mL	0.5590 mL	1.3975 mL
	60 mM	0.0466 mL	0.2329 mL	0.4658 mL	1.1646 mL
	80 mM	0.0349 mL	0.1747 mL	0.3494 mL	0.8734 mL
	100 mM	0.0279 mL	0.1397 mL	0.2795 mL	0.6987 mL

PF 04531083 Related Classifications

Neurological Disease

Keywords:

PF 045310831079400-07-9PF04531083PF-04531083Sodium ChannelNa channelsNa+ channelsinflammationrespiratoryblood-brain barrierInhibitorinhibitorinhibit

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PF 04531083

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PF 04531083 Related Antibodies

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PF 04531083 Related Antibodies

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Complete Stock Solution Preparation Table

PF 04531083 Related Classifications

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